Ammonium Chloride → 5-[(2,5-Difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-4-methylpyridine-2-carboxamide

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Reaction Steps

To a solution of 5-[(2,5-difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-4-methylpyridine-2-carboxylic acid (211 mg, 0.50 mmol) obtained in Example 12 in N,N-dimethylformamide (5 ml), (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (390 mg, 0.75 mmol), 1-hydroxybenzotriazole (101 mg, 0.75 mmol), ammonium chloride (54 mg, 1.00 mmol), and N-ethyldiisopropylamine (0.348 ml, 2.00 mmol) were added in an argon atmosphere at room temperature. After stirring for 5 hours at room temperature, ethyl acetate and water were added to the reaction mixture, and the resulting mixture was washed with saturated aqueous ammonium chloride. The organic layer was dried over anhydrous sodium sulfate and filtered, then the filtrate was concentrated under reduced pressure, and the resulting residue was subjected to flash silica gel chromatography. The fraction obtained from an elution with hexane:ethyl acetate=7:3 was concentrated under reduced pressure, and the resulting residue was washed with a mixed solvent of ethanol and hexane, and was collected by filtration, to obtain the title compound (154 mg, 0.37 mmol, 73%) as a white solid.

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